We have performed a cross-sectional analysis of the relationship between prorenin values and the microvascular complications of diabetes in a well controlled population of insulin-dependent diabetes mellitus (IDDM) subjects. One hundred and thirty-nine subjects (75 men, 64 women, age 44 +/- 17 years; duration of diabetes 19 +/- 15 years), formed the study group. Sixty-seven subjects (48.2%) had no complications, 55 (39.6%) had retinopathy alone, and 17 (12.2%) had retinopathy and albuminuria. Patients with no complications had lower prorenin values than those with microvascular complications (p < 0.001), whilst patients with both albuminuria and retinopathy had higher values than those with retinopathy alone (p < 0.05). Retinopathy was associated with duration of diabetes (p < 0.0001), diastolic blood pressure (p < 0.02) and albuminuria (p < 0.0001) while albuminuria was associated with prorenin (p < 0.02), serum triglyceride (p < 0.01) and retinopathy (p < 0.001). Patients with albuminuria were 5.5 times more likely to have raised prorenin values (>80 ng/mL/h) than those with normal albumin excretion [95% confidence interval (CI): 1.48-20.12] and those with retinopathy alone were 2.5 times as likely (95% CI: 1.19-5.15). Eighty patients with IDDM (40 males, 40 females; age: 47 +/- 17 years; duration of diabetes: 20 +/- 15 years), had retinal photography performed to determine the association between the severity of retinopathy and prorenin values. Retinopathy was more severe in patients with retinopathy and albuminuria than in those with retinopathy alone (p < 0.002). When the prorenin values of patients with more marked retinopathy (eye grade greater than 3) were compared, prorenin values of those with retinopathy and albuminuria were greater than those of patients with retinopathy alone [269 (139-1406) versus 91 (41-273) ng/mL/h: geometric mean (range); p < 0.05]. Furthermore, when patients without albuminuria were considered, there was no significant difference between the prorenin levels of patients with more severe retinopathy (eye grade >3) when compared to patients with lesser degrees of retinopathy [91 (41-273) versus 69 (23-375). In patients with microvascular complications, prorenin values were independently predicted by albuminuria (p < 0.0001) and diastolic blood pressure (p < 0.02) but not the severity of retinopathy. In conclusion, prorenin values are significantly associated with the presence of microvascular complications in patients with IDDM. The association with albuminuria may be stronger than the association with retinopathy.